Injury to the nervous system can produce some of the most debilitation health conditions in patients. These conditions or the loss of billions of dollars worth of productivity and the attendant health states can result in excruciating pain, immobility and other forms of human suffering. Currently millions of people throughout the industrialized, developing and undeveloped countries of the world are being adversely affected.
The nervous system is comprised of nerves, ganglia, spinal cord, brain and retina and consists of glial and neuronal cells, which number in the trillions. Neurons are considered the main cell type responsible for the complex functions associated with the nervous system. Neurons require energy in the form of ATP (adenosine triphosphate) to survive and carry out their functions. The production and maintenance of energy supply inside neurons requires a fuel source such as glucose, cofactors and vitamins, oxygen, and an energy buffering system to utilize ATP efficiently. Applicants have discovered that the specific combination of pyruvate as a fuel source, nicotinamide as a precursor of the cofactor NAD and creatine as a neuronal energy buffering agent provides a minimal combination to increase neuronal energy levels. All three of these agents also happen to have additional pharmacological actions, which help protect neurons from a wide variety of injuries. Unexpectedly, the combination of these agents provides a novel synergistic effect which benefits the neurons in combating injurious biochemical events while at the same time raising cellular energy levels. To maximize the delivery of all three agents to the brain we also define a strategy to enhance local brain pyruvate production using orally administered aminoacids.
Over the past 2 decades a wealth of new information has elucidated many of the fundamental biochemical events that mediate cell injury and death during brain insults such as stroke, trauma, epilepsy and during the progression of neurodegenerative diseases such as Parkinson's, Alzheimer's, and Huntington's disease. Several fundamental injury mechanisms, in fact, appear to play a prominent role in all of these diverse clinical conditions (see the attached review for a detailed survey of the role of these mechanisms in traumatic brain injury). Most prominent among the brain injury mechanisms involved in both acute and chronic brain insults or diseases are: a) oxidative stress in which excessive free radicals are produced, b) an overload of calcium inside the cell cytoplasm, and c) glutamate-mediated excitotoxicity. All three of these events compromise neuronal energy supply (see FIG. 1).